Nivolumab During Active Surveillance After Neoadjuvant Chemoradiation for Esophageal Cancer: SANO-3 Study

NCT05491616 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: CA209-6KC
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

In an effort to prevent surgery in selected patients with esophageal cancer, the SANO-2 study offers active surveillance to patients with clinically complete response (cCR) after neoadjuvant chemoradiation (nCRT). Some of these patients will never develop locoregional and/or distant recurrence of disease (persistent cCR). However, two-thirds of the patients that undergo active surveillance still get disease recurrence. This can be locoregional regrowth or distant metastases. To increase the efficacy of active surveillance (reduce the proportion of patients that need surgery) and improve survival, effective systemic maintenance therapy is needed. The CheckMate 577 randomized, placebo controlled, clinical trial showed that Nivolumab increases disease free survival in patients after nCRT and esophagectomy. Objective: To assess the efficacy of nivolumab during active surveillance in patients with cCR after neoadjuvant chemoradiation for esophageal cancer

Conditions

Esophageal Cancer

Keywords

immunotherapy; Nivolumab

Outcome Measures

Primary Outcomes (1)

• Disease Free survival 18 months

  No locoregional or distant recurrence of disease, evaluated by PETCT, EUS (Endoscopic Ultrasound), endoscopy + bite-on-bite biopsy

  18 months

Secondary Outcomes (4)

• the proportion of patients with locoregional and/or distant metastase

  occurence or end of follow-up (2 years after start immunotherapy), which comes first

• the proportion of patients that undergo esophagectomy

  occurence or end of follow-up (2 years after start immunotherapy), which comes first

• health-related quality of life (HRQOL) at baseline, 3, 6, 12 and 24 months after inclusion

  baseline, 3, 6, 12 and 24 months after inclusion

• overall survival at 2 years

  2 years

Study Arms (1)

Nivolumab q4w

EXPERIMENTAL

patients will receive Nivolumab at 480mg Q4W starting 10-14 weeks

Drug: Nivolumab

Interventions

Nivolumab DRUG

In this SANO-3 study, patients will receive Nivolumab at 480mg Q4W starting 10-14 weeks after nCRT (i.e., when cCR has been established) until disease progression or unacceptable toxicity, for a maximum duration of 1 year.

Also known as: Immune Checkpoint Inhibitor

Nivolumab q4w

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18
• Written informed consent and ability to understand the nature of the study and the study-related procedures and to comply with them
• Pre-treatment stage cT2-4aN0-2M0 disease. In case of stage cT4a, the possibility for a curative resection has to be explicitly verified by the multidisciplinary tumor board
• nCRT (CROSS regimen) completed, i.e. all radiotherapy fractions administered.
• Complete clinical response 10-14 weeks after nCRT as determined by endoscopy with biopsies, EUS with FNA and PET/CT scanning
• No prior cytotoxic chemotherapy other than as part of the neoadjuvant chemoradiation (CROSS)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Adequate cardiac function (cardiac function tests such as echocardiography only necessary in symptomatic patients).
• Adequate respiratory function (pulmonary function tests only necessary in symptomatic patients).
• Adequate renal function (Glomerular Filtration Rate \>40 ml/min) or Serum creatinine \<=1.5 x upper limit of normal (ULN)
• Adequate liver function (AST and ALT \< 3.0 x ULN; Total bilirubin \< 1.5 x ULN (except participants with Gilbert Syndrome who may have a total bilirubin level of \< 3.0 x ULN)
• Women of child-bearing potential must have a negative serum pregnancy test during screening period
• Patients must be willing to use adequate contraception during the study and for 3 months after the end of the study.

You may not qualify if:

• Language difficulty, dementia or altered mental status prohibiting the understanding and giving of informed consent and to complete quality of life questionnaires;
• Patients who were treated with definitive chemoradiotherapy
• Patients who were unable to complete all radiotherapy fractions of the nCRT
• No cCR at 10-14 weeks
• Esophageal cancer evaluated as not curatively-resectable by the multidisciplinary tumour board, for instance because ingrowth in the trachea, aorta or vertebra (cT4b)
• Gastric carcinoma
• Clinically significant (active) cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months)
• Clinically significant lung disease (Forced Expiratory Volume in one second (FEV1)
• Pregnant and lactating women, or patients of reproductive potential who are not using effective birth control methods. If barrier contraceptives are used, they must be continued by both sexes throughout the study.
• Participation, current or during the last 30 days prior to informed consent, in another intervention trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention of this study.
• Expected lack of compliance with the protocol
• Refusal to undergo further active surveillance (i.e., opting for esophageal resection)
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured or successfully resected, such as basal or squamous cell skin cancer, superficial bladder cancer, or GC, or carcinoma in situ of the prostate, cervix, or breast
• Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
• Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents for adults, or \> 0.25 mg/kg daily prednisone equivalent for adolescent) or other immunosuppressive medications within 14 days of study treatment. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents for adults, or \> 0.25 mg/kg daily prednisone equivalent for adolescents are permitted, in the absence of active autoimmune disease.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC

Rotterdam, 3015GD, Netherlands

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Nivolumab; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Bianca Mostert, MD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 2, 2022
• First Posted: August 8, 2022
• Study Start: September 29, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 13, 2025

Record last verified: 2025-02

Locations

NL (1)